Effect of Burosumab on the Inflammatory Profile of Patients With X-linked Hypophosphatemic Rickets FLAM-XLH
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 20
- 主要终点
- Expression of inflammatory markers (Il6, Il8, Il1β, CXCL1, CCL2, CXCR3, Il1R, Il6R) obtained from circulating monocytic cells of XLH patients treated with burosumab, before and 7 days after injection.
研究概览
简要总结
X-linked hypophosphataemia (XLH) is a rare genetic disorder associated with increased circulating levels of the hormone FGF23, most commonly through mutation of the PHEX gene. XLH is associated with a wide range of clinical manifestations in children and adults, all of which can impact on their health-related quality of life.
Conventional treatment (or standard of care, SOC) consists of phosphate supplementation and active vitamin D analogues. The management of patients with XLH has been modified in France since 2018 with the authorisation of the anti-FGF23 antibody, burosumab, in paediatrics (and in 2020 in adults).
A propensity for overweight/obesity has recently been demonstrated in these patients. Could extra-skeletal effects of FGF23, in particular on the inflammatory profile of patients, be responsible for these manifestations? Obesity has been associated with inflammation in other populations. In terms of inflammation, there is a close link between FGF23 and inflammation: inflammatory cytokines increase the production of FGF23, which in turn increases inflammation by stimulating the production of inflammatory cytokines. Osteoclastogenesis and inflammation are linked and inflammation has been shown to increase bone resorption.
In a recent study, the investigators showed that osteoclastogenesis was significantly impaired in cells obtained from XLH patients compared with control patients, and that osteoclasts obtained from XLH children showed higher gene expression of inflammatory markers than controls. Interestingly, no difference was observed in circulating monocytic cells between the two patient subgroups, conservative treatment and burosumab, whereas the inflammatory profile at the end of osteoclastic differentiation was reduced in cells derived from patients receiving burosumab.
The aim of this study is therefore to investigate the inflammatory profile of circulating monocytic cells on the day of burosumab injection (D0) and seven days later (peak effect of anti-FGF23).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 0 Years 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children and adults with genetically confirmed XLH followed at the Lyon Reference Centre for Rare Calcium, Phosphorus and Magnesium Diseases
- •Patients treated with Burosumab
- •Patients >12 kg.
- •Patients and parent/guardian who have been informed of the study and who do not object to participate
排除标准
- •Patients undergoing treatment with oral corticosteroids, or who have received more than 3 months of corticosteroid therapy in the past.
- •Patients who have received or are currently receiving immunosuppressive therapy.
- •Patients suffering from an inflammatory disease
- •Pregnant or breast-feeding women
- •Persons deprived of their liberty by judicial or administrative decision
- •Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
结局指标
主要结局
Expression of inflammatory markers (Il6, Il8, Il1β, CXCL1, CCL2, CXCR3, Il1R, Il6R) obtained from circulating monocytic cells of XLH patients treated with burosumab, before and 7 days after injection.
时间窗: Day 7
次要结局
未报告次要终点